In cirrhosis, abnormal persistent vasodilation of arterial vessels leads to increased portal venous inflow and contributes to portal hypertension. Indeed, portal hypertension is determined by both the degree of hepatic outflow resistance, related to liver architecture changes, and the extent of inflow into the portal venous system from the splanchnic bed. Portal hypertension is a major factor in the development of complications of cirrhosis, and as arterial vasodilation associated with portal hypertension is potentially reversible, understanding its mechanisms is of great therapeutic interest1. The gold-standard for assessing portal hypertension is currently hepatic venous pressure gradient measurement. However, this technique is invasive and available only in expert centres. Thus, there is a strong need for developing non-invasive techniques to help physicians for determining whether a patient with cirrhosis is at risk of having clinically significant portal hypertension (de Franchis, Journal of Hepatology 2010 vol. 53 j 762-768).
Vasodilation is associated with both enhanced formation of vasodilators, and vascular hyporesponsiveness to vasoconstrictors, also referred as to “vascular hypocontractility”. Nitric oxide (NO) overproduction cannot fully account for this effect, and several studies including those in endothelial nitric oxide synthase (NOS-3) knockout mice have shown that other factors are involved in the pathogenesis of arterial vasodilation. However, little is known about these factors, and more importantly, the mechanisms leading to vascular hypocontractility have not yet been elucidated1.
Microparticles (MPs) are membrane vesicles with a diameter ranging from 0.1 to 1 μm, released in extracellular space following cell activation or apoptosis2. MPs harbor at their surface most of the membrane-associated proteins of the cells they stem from and are characterized by the loss of plasma membrane asymmetry resulting in the exposure of phosphatidylserine on their outer leaflet2. MPs are present in the blood of healthy subjects and their levels are increased in patients with high atherothrombotic risk2. MPs are not inert by-products. A number of studies point out that MPs can affect several cellular functions, including vascular tone and vascular reactivity2. However, these studies were performed using MPs generated in vitro or isolated from patients with cardiovascular diseases or sepsis2.